EP0920868A1 - Eine kondensierte pyridazinverbindung enthaltendes heilmittel fuer erektionsstoerungen - Google Patents

Eine kondensierte pyridazinverbindung enthaltendes heilmittel fuer erektionsstoerungen Download PDF

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Publication number
EP0920868A1
EP0920868A1 EP97934748A EP97934748A EP0920868A1 EP 0920868 A1 EP0920868 A1 EP 0920868A1 EP 97934748 A EP97934748 A EP 97934748A EP 97934748 A EP97934748 A EP 97934748A EP 0920868 A1 EP0920868 A1 EP 0920868A1
Authority
EP
European Patent Office
Prior art keywords
optionally substituted
chloro
amino
methoxybenzyl
ring
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Withdrawn
Application number
EP97934748A
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English (en)
French (fr)
Other versions
EP0920868A4 (de
Inventor
Nobuhisa Watanabe
Yasuhiro Kabasawa
Shinya Abe
Mayu Shibazaki
Hiroki Ishihara
Kohtarou Kodama
Hideyuki Adachi
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Eisai Co Ltd
Original Assignee
Eisai Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Eisai Co Ltd filed Critical Eisai Co Ltd
Publication of EP0920868A1 publication Critical patent/EP0920868A1/de
Publication of EP0920868A4 publication Critical patent/EP0920868A4/de
Withdrawn legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/50—Pyridazines; Hydrogenated pyridazines
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
    • C07D237/26—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings condensed with carbocyclic rings or ring systems
    • C07D237/30—Phthalazines
    • C07D237/34—Phthalazines with nitrogen atoms directly attached to carbon atoms of the nitrogen-containing ring, e.g. hydrazine radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/06—Antiabortive agents; Labour repressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A61P15/10—Drugs for genital or sexual disorders; Contraceptives for impotence

Definitions

  • the present invention relates to remedies for erectile dysfunction which contain as the active ingredient novel fused pyridazine compounds.
  • Erectile dysfunction arises when at least one of these conditions is inhibited.
  • the urological treatments for erectile dysfunction effected today involve drug therapy and operative penile prosthesis with the use of penile prosthetic appliances.
  • the ring C represents an unsaturated 5 or 6 membered ring optionally having hetero atom(s);
  • n is 0 or an integer of from 1 to 4;
  • R 1 represents a halogen, an optionally substituted lower alkyl, an optionally substituted lower alkoxy, an optionally substituted cycloalkyl, a nitro, a cyano, a group represented by the formula -NR 2 R 3 (wherein R 2 and R 3 are the same as or different from each other and represent a hydrogen, an optionally substituted lower alkyl, an acyl, an optionally substituted arylalkyl or an optionally substituted heteroary
  • the present invention further provides: (2) remedies for female sexual dysfunction, dysmenorrhea or premature birth comprising as the active ingredient the above fused pyridazine compounds or pharmacologically acceptable salts thereof; (3) medicinal compositions comprising a therapeutically effective dose of the above fused pyridazine compounds or pharmacologically acceptable salts thereof and pharmacologically acceptable carriers; (4) a method for treating erectile dysfunction, female sexual dysfunction, dysmenorrhea or premature birth which comprises administering a therapeutically effective dose of the above fused pyridazine compounds or pharmacologically acceptable salts thereof to a patient with erectile dysfunction, female sexual dysfunction or dysmenorrhea or a patient giving premature birth; and (5) use of the above fused pyridazine compounds or pharmacologically acceptable salts thereof for producing remedies for erectile dysfunction, female sexual dysfunction, dysmenorrhea or premature birth.
  • the unsaturated 5 or 6 membered ring optionally having hetero atom(s) represented by the ring C benzene, pyridine, pyrazine, pyrimidine, pyridazine, pyrrole, imidazole, pyrazole, thiophene and furan rings may be proposed.
  • the lower alkyl in the "optionally substituted lower alkyl" as used in the definition of R 1 , R 1a , R 1b , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 and R 13 means linear or branched C 1-6 alkyl such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-methylpropyl, tert-butyl, n-pentyl, 1-ethylpropyl, isoamyl and n-hexyl.
  • substituents examples include hydroxy, nitro, amino, cyano, acyl such as acetyl and benzoyl, lower alkoxy such as methoxy and ethoxy, halogeno such as fluorine, chlorine, bromine and iodine and optionally protected carboxy. Either one or more of these substituents may be attached to one or more carbon atoms in the lower alkyl.
  • the lower alkoxy in the "optionally substituted lower alkoxy" as used in the definition of R 1 , R 1a and R 1b means those derived from the above-mentioned lower alkyl, for example, methoxy, ethoxy and propoxy.
  • substituents include hydroxy, nitro, amino, cyano, acyl such as acetyl and benzoyl, lower alkoxy such as methoxy and ethoxy, halogeno such as fluorine, chlorine, bromine and iodine, and optionally protected carboxy. Either one or more of these substituents may be attached to one or more carbon atoms in the lower alkoxy.
  • the cycloalkyl in the "optionally substituted cycloalkyl" as used in the definition of R 1 , R 1a and R 1b means C 3-8 ones.
  • substituents include hydroxy, nitro, amino, cyano, acyl such as acetyl and benzoyl, lower alkoxy such as methoxy and ethoxy, halogeno such as fluorine, chlorine, bromine and iodine, and optionally protected carboxy. Either one or more of these substituents may be attached to one or more carbon atoms in the cycloalkyl.
  • acyl as used in the definition of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 12 and R 13 means acyl derived from aliphatic, aromatic or heterocyclic groups. Examples thereof include lower alkanoyl such as formyl, acetyl, propionyl, butyryl, valeryl, isovaleryl and pivaloyl, aroyl such as benzoyl, toluoyl and naphthoyl, and heteroaroyl such as furoyl, nicotinoyl and isonicotinoyl. Namely, any groups derived from various carboxylic acids are involved therein. Among these substituents, it is preferable to use formyl, acetyl, benzoyl, etc.
  • aryl in the "optionally substituted aryl" as used in the definition of A and B means those derived from aromatic rings such as phenyl, 1-naphthyl, 2-naphthyl and anthracenyl.
  • substituents include hydroxy, nitro, amino, cyano, acyl such as acetyl and benzoyl, lower alkoxy such as methoxy and ethoxy, halogeno such as fluorine, chlorine, bromine and iodine, and optionally protected carboxy.
  • heteroaryl in the "optionally substituted heteroarylalkyl" as used in the definition of A and B means monocyclic or heterocyclic groups containing one or more atoms of nitrogen, sulfur, oxygen, etc. Examples thereof include pyridyl, pyrrolyl, imidazolyl, pyrazolyl, pyrazyl, pyrimidyl, pyridazyl, thienyl, pyranyl, isothiazolyl, isoxazolyl, furazanyl, benzothienyl, furyl, indolyl, indolizinyl, isoindolyl, benzothiazolyl, benzimidazolyl and quinazolyl.
  • substituents examples include hydroxy, nitro, amino, cyano, acyl such as acetyl and benzoyl, lower alkoxy such as methoxy and ethoxy, halogeno such as fluorine, chlorine, bromine and iodine, and optionally protected carboxy.
  • R 2 and R 3 , R 4 and R 5 , or R 7 and R 8 together with the nitrogen atom to which they are bonded may form a ring
  • R 2 and R 3 , R 4 and R 5 , or R 7 and R 8 may form, together with the nitrogen atom to which they are bonded, for example, piperidinyl, pyrrolidinyl, piperazinyl, etc.
  • substituents examples include hydroxy, optionally substituted amino, aminoalkyl, nitro, nitroalkyl, lower alkoxy, lower alkoxyalkyl, hydroxyalkyl, optionally protected carboxy and optionally protected carboxyalkyl.
  • the most preferable examples of the substituent include hydroxy, hydroxymethyl, hydroxyethyl, carboxymethyl and carboxyethyl.
  • the aryl in the "optionally substituted arylalkyl" as used in the definition of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 and Y means those derived from aromatic rings such as phenyl, 1-naphthyl, 2-naphthyl and anthracenyl.
  • the alkyl as used herein means those derived from the above-mentioned lower alkyl.
  • substituents examples include hydroxy, nitro, amino, cyano, acyl such as acetyl and benzoyl, lower alkoxy such as methoxy and ethoxy, halogeno such as fluorine, chlorine, bromine and iodine, and optionally protected carboxy.
  • heteroaryl in the "optionally substituted heteroarylalkyl" as used in the definition of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 12 , R 13 and Y means monocyclic or heterocyclic groups containing one or more atoms of nitrogen, sulfur, oxygen, etc.
  • Examples thereof include pyridyl, pyrrolyl, imidazolyl, pyrazolyl, pyrazyl, pyrimidyl, pyridazyl, thienyl, pyranyl, isothiazolyl, isoxazolyl, furazanyl, benzothienyl, furyl, indolyl, indolizinyl, isoindolyl, benzothiazolyl, benzimidazolyl and quinazolyl.
  • the alkyl as used herein manes those derived from the above-mentioned lower alkyl.
  • substituents examples include hydroxy, nitro, amino, cyano, acyl such as acetyl and benzoyl, lower alkoxy such as methoxy and ethoxy, halogeno such as fluorine, chlorine, bromine and iodine, and optionally protected carboxy.
  • halogeno as used in the definition of R 1 , R 1a , R 1b , R 12 , R 13 and R 14 means fluorine, chlorine, bromine, iodine, etc.
  • Examples of the pharmacologically acceptable salts to be used in the present invention include inorganic acid salts such as hydrochlorides, sulfates, hydrobromides and phosphates and organic acid salts such as formates, acetates, trifluoroacetates, maleates, fumarates, tartrates, methanesulfonates, benzenesulfonates and toluenesulfonates.
  • inorganic acid salts such as hydrochlorides, sulfates, hydrobromides and phosphates
  • organic acid salts such as formates, acetates, trifluoroacetates, maleates, fumarates, tartrates, methanesulfonates, benzenesulfonates and toluenesulfonates.
  • pyridazine compounds represented by the following formula (I) wherein the ring C is benzene or pharmacologically acceptable salts thereof: (wherein n, R 1 , A, X, Y and are each as defined above).
  • fused pyridazine compounds or pharmacologically acceptable salts thereof can be percutaneously, intravenously or orally administered for treatment without resort to injection directly into the penile cavernosum, which makes them favorable as remedies for erectile dysfunction.
  • the compounds of the present invention may be administered in an arbitrary dose without restriction, they are usually given to an adult in a dose of from 5 ⁇ g to 100 mg, preferably from 10 to 1,000 ⁇ g, in the case of intravenous administration, or in a dose of from 1 to 1,000 mg, preferably from 5 to 100 mg, in the case of oral administration.
  • WO96/05176 discloses processes for producing these fused pyridazine compounds or pharmacologically acceptable salts thereof and their phosphodiesterase type V inhibitory activities.
  • the compounds of the present invention aim at treating male erectile dysfunction, these compounds are also efficacious against female sexual dysfunction, premature birth and dysmenorrhea.
  • the penis was extirpated from a Japanese white rabbit (about 3 kg) under anesthesia with pentobarbital (50 mg/kg) administered intravenously to give a penile cavernosum preparation (about 20 ⁇ 1.5 ⁇ 1.5 mm).
  • This preparation was suspended in a Magnus tube filled up with Krebs-Henseleit's nutritive solution (containing 1 ⁇ M of indomethacin) at 37°C and a gas mixture (95% oxygen + 5% carbon dioxide) was bubbled thereinto. Then the isometric tension was recorded under a load of 2 g. To stabilize the contraction, contraction caused by adding a potassium chloride solution (final concentration: 50 mM) and washing with the nutritive solution were repeated for two times.
  • a potassium chloride solution final concentration: 50 mM
  • the preparation was contracted by adding a phenylephrine solution (final concentration: 10 ⁇ M).
  • a phenylephrine solution final concentration: 10 ⁇ M.
  • 4-(3-chloro-4-methoxybenzyl)amino-6-cyano-l-(4-hydroxypiperidino)-phthalazine hydrochloride (hereinafter referred to as the compound A) was added cumulatively at a common ratio of 10 from 1 nM to 100 ⁇ M in the final concentration and the tension was continuously recorded. From the dose-response curve thus formed, the medium relaxation concentration of the compound A on the contraction was determined. The value obtained from six preparations was 4.47 ⁇ M (95% confidence limit: 1.88 - 10.6 ⁇ M). Conc. ( ⁇ M) of Compound A Relaxation ratio (%) 0.01 17.4 ⁇ 1.4 0.1 28.1 ⁇ 5.1 1.0 40.8 ⁇ 10.4 10.0 61.4 ⁇ 5.1 100.0 90.6 ⁇ 1.6
  • 6-cyano-2,3-dihydro-1,4-phthaladinedione was suspended in 400 ml of phosphorus oxychloride. After adding 75 ml of diisopropylethylamine, the mixture was heated under reflux for 40 minutes. Then the excessive phosphorus oxychloride was evaporated and the residue was dissolved in methylene chloride and poured into ice water. After filtering off the unnecessary through celite, the celite filter was washed with methylene chloride. The filtrate was extracted with methylene chloride. The organic layer was washed with a saturated aqueous solution of sodium bicarbonate, dilute hydrochloric acid and brine and dried over anhydrous magnesium sulfate. This solution was filtered by using silica gel and the solvent was evaporated to give 66 g of 6-cyano-1,4-dichlorophthalazine as a pale orange solid.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Reproductive Health (AREA)
  • Endocrinology (AREA)
  • Engineering & Computer Science (AREA)
  • General Chemical & Material Sciences (AREA)
  • Gynecology & Obstetrics (AREA)
  • Pregnancy & Childbirth (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Plural Heterocyclic Compounds (AREA)
EP97934748A 1996-08-20 1997-08-08 Eine kondensierte pyridazinverbindung enthaltendes heilmittel fuer erektionsstoerungen Withdrawn EP0920868A4 (de)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
JP21820496 1996-08-20
JP21820496 1996-08-20
PCT/JP1997/002785 WO1998007430A1 (fr) 1996-08-20 1997-08-08 Medicament contre les defaillances de l'erection, renfermant un compose a base de pyridazine fondue

Publications (2)

Publication Number Publication Date
EP0920868A1 true EP0920868A1 (de) 1999-06-09
EP0920868A4 EP0920868A4 (de) 2004-05-26

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EP97934748A Withdrawn EP0920868A4 (de) 1996-08-20 1997-08-08 Eine kondensierte pyridazinverbindung enthaltendes heilmittel fuer erektionsstoerungen

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Country Link
US (1) US6288064B1 (de)
EP (1) EP0920868A4 (de)
KR (1) KR100485249B1 (de)
CN (1) CN1121220C (de)
AU (1) AU722710B2 (de)
CA (1) CA2258079A1 (de)
HU (1) HUP9903168A3 (de)
NO (1) NO318114B1 (de)
NZ (1) NZ333354A (de)
WO (1) WO1998007430A1 (de)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999042452A1 (fr) 1998-02-19 1999-08-26 Eisai Co., Ltd. Derives de phtalazine et remedes contre la dyserection
WO2000026218A1 (en) * 1998-10-29 2000-05-11 Zambon Group S.P.A. Tricyclic phthalazine derivatives as phosphodiesterase 4 inhibitors
EP1165521A4 (de) * 1999-03-22 2002-05-22 Bristol Myers Squibb Co Kondensierte pyridopyridazine als inhibitoren der cgmp-phosphodiesterase
US6689883B1 (en) 1999-09-28 2004-02-10 Bayer Pharmaceuticals Corporation Substituted pyridines and pyridazines with angiogenesis inhibiting activity
US6903101B1 (en) 2000-08-10 2005-06-07 Bayer Pharmaceuticals Corporation Substituted pyridazines and fused pyridazines with angiogenesis inhibiting activity
US7977333B2 (en) 2000-04-20 2011-07-12 Bayer Healthcare Llc Substituted pyridines and pyridazines with angiogenesis inhibiting activity

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6326379B1 (en) 1998-09-16 2001-12-04 Bristol-Myers Squibb Co. Fused pyridine inhibitors of cGMP phosphodiesterase
EP1120120A4 (de) * 1998-10-05 2009-04-29 Eisai R&D Man Co Ltd Tableten die sich unmittelbar in der mundhöhle auflösen
CZ20012020A3 (cs) * 1998-12-07 2001-10-17 Nissan Chemical Industries, Ltd. Činidlo pro léčbu erektilní dysfunkce
US6576644B2 (en) 2000-09-06 2003-06-10 Bristol-Myers Squibb Co. Quinoline inhibitors of cGMP phosphodiesterase
US7759337B2 (en) * 2005-03-03 2010-07-20 Amgen Inc. Phthalazine compounds and methods of use
CA2643044A1 (en) * 2006-02-28 2007-09-07 Amgen Inc. Cinnoline and quinazoline derivates as phosphodiesterase 10 inhibitors
WO2010042646A1 (en) 2008-10-10 2010-04-15 Amgen Inc. Aza- and diaza-phthalazine compounds as p38 map kinase modulators and methods of use thereof
WO2010042649A2 (en) 2008-10-10 2010-04-15 Amgen Inc. PHTHALAZINE COMPOUNDS AS p38 MAP KINASE MODULATORS AND METHODS OF USE THEREOF
EP2379076B1 (de) 2008-12-23 2014-11-12 The Trustees of Columbia University in the City of New York Phosphodiesterase-hemmer und ihre verwendungen
US9594736B2 (en) * 2013-10-11 2017-03-14 Apple Inc. Display and selection of bidirectional text
JP2017511797A (ja) 2014-02-18 2017-04-27 ビーエーエスエフ ソシエタス・ヨーロピアＢａｓｆ Ｓｅ Ｎ−エチルジイソプロピルアミンの製造方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4289772A (en) * 1977-06-03 1981-09-15 Pfizer Inc. 1-Piperidinophthalazines as cardiac stimulants
EP0449203A1 (de) * 1990-03-30 1991-10-02 Mitsubishi Chemical Corporation 4-Phenylphthalazin-Derivate
EP0722936A1 (de) * 1994-08-09 1996-07-24 Eisai Co., Ltd. Kondensierte pyridazinverbindungen

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5187180A (en) * 1990-07-26 1993-02-16 Merck Frosst Canada, Inc. (quinolin-2-ylmethoxy)heterotetrahydrocarbazoles as inhibitors of the biosynthesis of leukotrienes
JPH08143558A (ja) * 1994-11-21 1996-06-04 Fujisawa Pharmaceut Co Ltd アミノピペラジン誘導体の新規医薬用途
GB9423910D0 (en) * 1994-11-26 1995-01-11 Pfizer Ltd Therapeutic agents

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4289772A (en) * 1977-06-03 1981-09-15 Pfizer Inc. 1-Piperidinophthalazines as cardiac stimulants
EP0449203A1 (de) * 1990-03-30 1991-10-02 Mitsubishi Chemical Corporation 4-Phenylphthalazin-Derivate
EP0722936A1 (de) * 1994-08-09 1996-07-24 Eisai Co., Ltd. Kondensierte pyridazinverbindungen

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
BOOLELL M ET AL: "SILDENAFIL: AN ORALLY ACTIVE TYPE 5 CYCLIC GMP-SPECIFIC PHOSPHODIESTERASE INHIBITOR FOR THE TREATMENT OF PENILE ERECTILE DYSFUNCTION" INTERNATIONAL JOURNAL OF IMPOTENCE RESEARCH, STOCKTON, BASINGSTOKE, GB, vol. 8, no. 2, June 1996 (1996-06), pages 47-52, XP000938747 ISSN: 0955-9930 *
See also references of WO9807430A1 *

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999042452A1 (fr) 1998-02-19 1999-08-26 Eisai Co., Ltd. Derives de phtalazine et remedes contre la dyserection
WO2000026218A1 (en) * 1998-10-29 2000-05-11 Zambon Group S.P.A. Tricyclic phthalazine derivatives as phosphodiesterase 4 inhibitors
EP1165521A4 (de) * 1999-03-22 2002-05-22 Bristol Myers Squibb Co Kondensierte pyridopyridazine als inhibitoren der cgmp-phosphodiesterase
US6689883B1 (en) 1999-09-28 2004-02-10 Bayer Pharmaceuticals Corporation Substituted pyridines and pyridazines with angiogenesis inhibiting activity
US7977333B2 (en) 2000-04-20 2011-07-12 Bayer Healthcare Llc Substituted pyridines and pyridazines with angiogenesis inhibiting activity
US6903101B1 (en) 2000-08-10 2005-06-07 Bayer Pharmaceuticals Corporation Substituted pyridazines and fused pyridazines with angiogenesis inhibiting activity

Also Published As

Publication number Publication date
HUP9903168A2 (hu) 2000-05-28
KR20000065260A (ko) 2000-11-06
KR100485249B1 (ko) 2005-09-09
WO1998007430A1 (fr) 1998-02-26
NO990805D0 (no) 1999-02-19
NZ333354A (en) 2000-05-26
HUP9903168A3 (en) 2002-01-28
CN1225586A (zh) 1999-08-11
NO990805L (no) 1999-04-16
US6288064B1 (en) 2001-09-11
EP0920868A4 (de) 2004-05-26
CN1121220C (zh) 2003-09-17
CA2258079A1 (en) 1998-02-26
AU3784897A (en) 1998-03-06
NO318114B1 (no) 2005-01-31
AU722710B2 (en) 2000-08-10

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